Zafirlukast is a tolyl compound and leukotriene receptor antagonist (LTRA), with anti-asthmatic and potential capsular contracture-preventing activities. Upon administration, zafirlukast selectively and competitively binds to and blocks the cysteinyl leukotriene 1 receptor (CYSLTR1), thereby preventing the potent pro-inflammatory mediator’s leukotriene C4, D4, and E4 from binding. This prevents leukotriene-mediated actions, including enhanced migration of eosinophils and neutrophils, increased adhesion of leukocytes, increased monocyte and neutrophil aggregation, increased airway edema, inflammation, capillary permeability, and bronchoconstriction. In addition, zafirlukast may decrease collagen deposition, fibrosis, and capsular thickness after implantation, thereby preventing scar tissue.
Zafirlukast is an orally administered leukotriene receptor antagonist (LTRA) used for the chronic treatment of asthma. While zafirlukast is generally well-tolerated, headache and stomach upset often occur. Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily.
Mechanism of Action of zafirlukast
Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4, and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited the inhaled LTD4-induced influx of eosinophils into animal lungs.
Indications of zafirlukast
- Asthma Bronchial
- Chronic Urticaria
- COPD
- Allergic rhinitis
- Asthma, maintenance
- Bronchospasm prophylaxis
- Asthma bronchial
- Exercise-induced bronchoconstriction
- Perennial allergic rhinitis
- Seasonal allergic rhinitis
- Prophylaxis and chronic treatment of asthma
- Relief of symptoms of seasonal allergic rhinitis and perennial allergic rhinitis
- Prevention of exercise-induced bronchoconstriction
- Prevent the narrowing of airways triggered by exercise
- Seasonal allergic rhinitis (hay fever) symptoms.
Contra-Indications of zafirlukast
- Mood Changes
- Having Thoughts of Suicide
- Feeling Agitated
- depression
- Hardening of the Liver
- liver problems
- Hallucination
- Chronic Trouble Sleeping
- Involuntary Quivering
- abnormal liver function tests
- Nervous
- Abnormal Dreams
- anxiety disorder
- Allergies to Zafirlukast & Leukotriene Receptor Antagonist
Dosages of zafirlukast
- Strengths: 10 mg; 20 mg
Asthma
- 20 mg orally twice a day, 1 hour before or 2 hours after meals
Pediatric Asthma
Less than 5 years
- The safety and effectiveness has not been established.
5 to 11 years
- 10 mg orally twice a day, 1 hour before or 2 hours after meals
12 years or older
- 20 mg orally twice a day, 1 hour before or 2 hours after meals
Maximum dosage
- 40 mg/day PO.
- 40 mg/day PO.
- 40 mg/day PO.
- 5—11 years: 20 mg/day PO.
- < 5 years: Safety and efficacy have not been established.
- Safety and efficacy have not been established.
Side Effects of zafirlukast
The most common
- a headache
- a sore throat
- a cough
- stomach pain
- A headache
- irritability
- restlessness
- sleeplessness
- unable to sleep
- stomach pain
- diarrhea
- dizziness, drowsiness
- upper respiratory tract infection.
- feeling unusually weak or tired
- upper respiratory tract infection.
Common
- agitation, including aggressive behavior and/or hostility
- tremor
- irritability, restlessness, feeling anxious
- depression
- Abdominal or stomach pain
- stomach pain
- nausea, vomiting
- diarrhea.
- agitation, including aggressive behavior and/or hostility
- irritability, restlessness, feeling anxious
- depression
- seeing, feeling or hearing things that are not there (also called hallucinations)
- dream abnormalities, difficulty sleeping
- sleepwalking.
- muscle aches or cramps, joint pain
- stomach pain
- nausea, vomiting
- diarrhea.
Rare
- Agitation
- anxiety
- breathing problems
- confusion about identity, place, and time
- constipation
- fast, irregular, pounding or racing heartbeat or pulse
- feeling sad or empty
- indigestion
- itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
- lack of appetite
- pains in the stomach, side, or abdomen, possibly moving to the back
- shaking or trembling of the hands or feet
Drug Interactions of zafirlukast
Zafirlukast may interact with following drugs, supplements & may change the efficacy of drugs
- antiseizure medications (e.g., clobazam, phenobarbital, phenytoin, valproic acid, )
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- Calcium channel blockers, diltiazem, verapamil
- domperidone
- famotidine
- carbamazepine
- carvedilol
- celecoxib
- ipratropium
- ketotifen
- levodopa
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- magnesium sulfate
- methylphenidate
- mirtazapine
- montelukast
- omeprazole
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine, citalopram)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- sotalol
- tapentadol
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, )
- thioridazine
- tolterodine
- tramadol
- trimethoprim
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- “triptan” migraine medications (e.g., eletriptan, sumatriptan)
- tryptophan
- tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
- theophylline
- trimethoprim
- warfarin
Pregnancy & Lactation of zafirlukast
FDA pregnancy category B
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
Zafirlukast passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.
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